The present invention relates to an artificial tube for nerve.
In the case of peripheral nerve being severed surgically or severed due to injury, an initial attempt is made to directly anastomose the stumps of the severed peripheral nerve. In many cases, however, it is impossible to accurately anastomose the severed nerve directly resulting in the nerve being left in the severed state. Consequently, although the nerve attempts to regenerate towards the distal side, it is impaired by connective tissue. Hence, regeneration stops with the formation of a neuroma at the severed end without reaching the neural stump on the distal side. As a result, the function of the severed nerve is frequently not restored after the surgical wound or injury has healed, and sequella remain. In cases in which direct anastomosis is impossible, a peripheral nerve having a function which is not very important may be partially excised from the same patient, and autotransplantation may be performed to the severed site of the nerve using this peripheral nerve segment. However, in this method as well, not only are there many cases in which nerve function is not adequately restored, but there are also many cases in which decreased function is observed even at the portion at which the transplanted nerve is used.
Therefore, numerous attempts have been made to restore function by connecting the stumps of severed peripheral nerves with a tube-shaped medical material, namely an artificial tube for nerve, regenerating the axon from the stump on the central side of the nerve trunk towards the stump on the distal side, inducing the nerve to extend in the proper direction, and allowing the nerve to reach a myoneural junction or peripheral sensory receptor from the peripheral nerve trunk. In the past, various materials have been attempted to be used as artificial tube for nerve, examples of which include non-porous tubes made of silicone, polyethylene or polyvinyl chloride, porous tubes made of drawn polytetrafluoroethylene or cellulose, semi-permeable membrane tubes made of polyacrylonitrile or polysulfone, tubes made of biodegradable materials such as polyglycolic acid, polylactic acid or their copolymers, gelatin tubes, or biological tissue tubes originating in the same species such as arteries and veins. However, in regeneration experiments on peripheral nerves using these materials, since biological repair is impaired by the material, the length of nerve that has been able to be regenerated thus far has been at most on the order of 15 mm. In addition, not only is the regenerated nerve narrow without the form of the nerve being normally restored, but there are also many cases in which the function of regenerated nerve is not restored. In addition, although examples have been reported in which neural growth factor NGF is filled into a tube, since NGF ends up rapidly running out of the tube and dispersing, remarkable effects have not been obtained.
Although artificial tubes for nerve which comprise collagen tubes in which collagen fibers on which laminin and fibronectin are coated are filled (Tong, X., et al., Brain Research 663: 155-162 (1994), have recently been attempted, since the collagen tubes are unable to remain without being broken down until the nerve is regenerated to an adequate length, satisfactory results have not been obtained.
On the other hand, the spinal cord is considered to not regenerate once it has been damaged. In the case the spinal cord is damaged due to injury or tumor, the damaged spinal cord does not regenerate, and all function below the damaged portion is lost with paralysis remaining as the sequella. Recently however, experiments on animals have begun to be conducted that prove that the spinal cord is also able to regenerate. In the case where the spinal cord is severed sharply and accurately re-sutured, function is restored and the damaged portion is repaired to a considerable degree. In addition, if a portion of the spinal cord is excised in the form of a tube and an intercostal nerve fasicle is implanted at that site, the portion of the spinal cord regenerates and function is at least partially restored. If a portion of the spinal cord is excised in the form of a tube, and fetal spinal cord is transplanted to that site, spinal cord function and form are restored. These findings have been observed in experiments in rats. In this case as well, it is recognized that regeneration occurs only in the case where the transplanted fetal spinal cord segment is transplanted by properly aligning the respective neural processes. Based on the above findings, although it has been determined that regeneration of the spinal cord can occur by inducing the spinal cord so as to properly align the compartments of regenerated tissue, there have been no artificial tubes for spinal cord developed whatsoever that actually allow spinal cord regeneration.
Therefore, in order to control the rate of decomposition in the body so as to remain in the body until the nerve regenerates while also allowing degradation and absorption in the body as nerve regeneration progresses, the development of an artificial tube for nerve is desired that induces axons regenerated from severed nerve stumps to extend in the proper direction without pressing on the regenerated nerve following nerve regeneration, and causes rapid restoration of blood flow by promoting infiltration of blood capillaries from the body to promote regeneration of nerve tissue. In addition, there is also an urgent need for the development of an artificial tube for spinal cord that connects not only peripheral nerves but also the missing portions of spinal cord, and promotes proper regeneration of spinal cord tissue along with restoration of function.
The present invention relates to an artificial tube for nerve which comprises tube 10 or 20 having a coating layer 13 or 23 composed of gelatin or collagen on at least the outer surface of tube 11 or 21 composed of a material that is biodegradable and absorbable in vivo, and a pre-thermal dehydration crosslinking treated collagen fiber bundle (referring to a bundle of fibers 31 composed of collagen) inserted in its lumen along the axis of said tube; wherein said fibers composed of collagen being coated with laminin. The present invention also relates to a method for producing the above-mentioned artificial tube for nerve comprising: preparing a bundle of pre-thermal dehydration crosslinking treated collagen fibers 31, coating the surface of each fiber 31 that composes said collagen fiber bundle with laminin, producing tube 10 or 20 having a coating layer 13 or 23 composed of gelatin or collagen on at least the outer surface of tube 11 or 21 composed of a material that is biodegradable and absorbable in vivo, inserting a collagen fiber bundle composed of said laminin-coated collagen in said tube so as to be substantially parallel to the axis of said tube, and performing thermal dehydration crosslinking treatment.